Ruthenium-Catalyzed Cycloaddition of Nitrile Oxides and Alkynes: Practical Synthesis of Isoxazoles

摘要

Isoxazoles, a major class of five-membered nitrogen hetero-cycles, are embedded in a number of pharmaceutically important compounds that have been the focus of numerous biological studies during the last several years. Although a variety of methods for their synthesis have been reported, few are general, regioselective, and high yielding. The cycloaddition of alkynes and nitrile oxides, which is probably the most direct route to access these heterocycles, is rarely used. The reasons for this are simple: in contrast to the reaction with olefins, the uncatalyzed, thermal cycloaddition reactions of nitrile oxides with alkynes are neither chemo- nor regioselective and, as a consequence, are plagued by low yields and the formation of multiple products. These shortcomings are not surprising considering the relatively high reactivity of nitrile oxides, their propensity to dimerize, and the general inert character of alkynes.